Yamaguchi Masayoshi
Division of Endocrinology and Metabolism and Lipids, Department of Medicine, Emory University School of Medicine, 101 Woodruff Circle, 1305 WMRB, Atlanta, GA 30322-0001, USA.
Mol Cell Biochem. 2009 Jul;327(1-2):53-63. doi: 10.1007/s11010-009-0042-4. Epub 2009 Feb 12.
RGPR-p117 was originally discovered as a novel protein that binds to a nuclear factor I (NFI) consensus motif TTGGC(N)(6)CC, which is present in the 5'-flanking region of the regucalcin gene (rgn). RGPR-p117 has been identified in human, rat, mouse, bovine, rabbit, and chicken livers. Phylogenetic analysis of six vertebrates shows that RGPR-p117 appears to form a single cluster, indicating a common evolutionary relationship of the RGPR-p117 family. The RGPR-p117 gene consists of at least 26 exons spanning approximately 4.1 kbp and is localized on human chromosome 1q25.2. RGPR-p117 mRNA is expressed in the liver, kidney, heart, spleen, and brain of rats. RGPR-p117 mRNA expression is stimulated through signaling mechanisms. Mammalian RGPR-p117 conserves a leucine zipper motif, which is present in many gene regulatory proteins. RGPR-p117 has been shown to translocate from the cytoplasm to the nucleus in NRK52E cells, a process which is mediated through protein kinase C signaling following hormonal stimulation. The phosphorylated RGPR-p117 binds to the TTGGC motif in the promoter region of the regucalcin gene and enhances regucalcin mRNA expression in the cells, indicating a role as a transcriptional factor. RGPR-p117 is also localized in the plasma membranes, nucleus, mitochondria, microsomes, and cytoplasm. Overexpression of RGPR-p117 has been found to induce a significant decrease in protein and DNA contents in cells, suggesting that RGPR-p117 may regulate the gene expression of other related proteins as well as the transcription factor. Also, overexpression of RGPR-p117 has a suppressive effect on cell death by inhibiting the gene expression of caspase-3, caspase-8, and Fas-associating death domain protein whose TTGGC motif is present in the promoter region of their genes. The novel protein RGPR-p117 has been shown to play an important role as a transcription factor.
RGPR-p117最初被发现是一种与核因子I（NFI）共有基序TTGGC(N)(6)CC结合的新型蛋白质，该基序存在于调节钙素基因（rgn）的5'侧翼区域。RGPR-p117已在人、大鼠、小鼠、牛、兔和鸡的肝脏中被鉴定出来。对六种脊椎动物的系统发育分析表明，RGPR-p117似乎形成了一个单一的聚类，表明RGPR-p117家族具有共同的进化关系。RGPR-p117基因由至少26个外显子组成，跨度约为4.1kbp，定位于人类染色体1q25.2。RGPR-p117 mRNA在大鼠的肝脏、肾脏、心脏、脾脏和大脑中表达。RGPR-p117 mRNA表达通过信号传导机制被刺激。哺乳动物RGPR-p117保留了一个亮氨酸拉链基序，许多基因调节蛋白中都存在该基序。已证明RGPR-p117在NRK52E细胞中从细胞质转移到细胞核，这一过程在激素刺激后通过蛋白激酶C信号传导介导。磷酸化的RGPR-p117与调节钙素基因启动子区域的TTGGC基序结合，并增强细胞中调节钙素mRNA的表达，表明其作为转录因子的作用。RGPR-p117也定位于质膜、细胞核、线粒体、微粒体和细胞质中。已发现RGPR-p117的过表达会导致细胞中蛋白质和DNA含量显著降低，这表明RGPR-p117可能调节其他相关蛋白质的基因表达以及转录因子。此外，RGPR-p117的过表达通过抑制其基因启动子区域存在TTGGC基序的半胱天冬酶-3、半胱天冬酶-8和Fas相关死亡结构域蛋白的基因表达，对细胞死亡具有抑制作用。新型蛋白质RGPR-p117已被证明作为转录因子发挥重要作用。
